Pipette tip handling devices and methods

ABSTRACT

Discussed herein are methods and devices for storing, handling, loading or dispensing of pipette tips. Some embodiments allow repetitive loading of an array of multiple pipette tips that are stored in a nested configuration.

RELATED PATENT APPLICATION

This patent application claims the benefit of U.S. Provisional PatentApplication No. 61/044,243, filed on Apr. 11, 2008, entitled PIPETTE TIPHANDLING DEVICES AND METHODS, naming Arta Motadel as an inventor. Theentire content of the foregoing patent application is herebyincorporated by reference, including all text, tables and drawings.

FIELD OF THE INVENTION

Described herein are method and device embodiments for storing, loadingor handling of pipette tips. Some embodiments allow for convenientloading of multiple batches of pipette tips into loading blocks orplates with a minimal amount of waste.

BACKGROUND

Pipette tips are used in large quantities for a wide variety ofapplications related to liquid material handling, such as measuring,dispensing and aspirating of the liquids. Pipette tips are often used inconjunction with hand held pipettors, such as mechanical or electricalpipettors, that have distal nozzles that are configured to be releasablyengaged with a proximal port or opening of a pipette tip in a sealedrelationship. The pipettor may then be used to apply a vacuum orotherwise decrease the pressure in the interior volume of the pipettetip in order to aspirate liquid into the pipette tip for transfer toanother location. For some applications a single pipettor may be used,however, for some applications, particularly automated or roboticapplications, pipettors or manifolds having multiple distal nozzles maybe used to engage multiple pipettor tips disposed in a loading plate orblock simultaneously.

For such configurations, after the pipette tips are seated onto thenozzles and removed from the loading block, a new set of pipette tipsmust be provided for the next cycle of liquid handling. Typically, a newset of pipette tips are taken from a package in a storage plate andloading block in a regularly spaced array and positioned for seatingwith the distal nozzles of the manifold. Because of the difficulty ofmanually handling large numbers of pipette tips due to the timeconsuming nature of such handling as well as the risk of contamination,pipette tips are generally pre-packaged in regularly spaced arraysspaced in pre-determined spacing to match the spacing of the array ofdistal nozzles. The pipette tips may be transferred from the packagingin a loading plate that is part of the packaging but may also include anentire loading plate and loading block in order to maintain the arrayconfiguration during handling and transfer to a location for seating tothe manifold or pipettor.

For such multiple pipette tip arrays, because each pipette tip mayrequire a significant amount of axial force between the respectivenozzle and proximal opening of the pipette tip in order to be properlyseated, the cumulative force required to seat an array of pipette tipsmay be quite high. For example, a 96 tip manifold may exert about 75pounds to about 250 pounds of force on a loading block having a 96 tiparray. Because of the amount of force generated, the loading block thatsupports the loading plate must be structurally strong and able towithstand the cumulative axial force without significant deformation. Tobe this strong, the block requires a significant amount of mass ofmaterial which is typically a polymer. Once the distal nozzles of themanifold have engaged and seated the pipette tips and withdrawn themfrom the loading plate and block, the loading block and plate aredisposed of and replaced with a new loading block and plate that is fullof new pipette tips. As a result, a user performing a high volume ofsuch liquid handling cycles will be disposing of a large volume ofloading blocks and plates which generates a large volume of polymerwaste which may be environmentally unsound in many instances.

For embodiments of pipette tip arrays that transfer in a loading platewithout the loading block, the loading tray is lifted or moved from thepackaging, as necessary, and positioned over a loading block. After eachseating of an array of pipette tips, the loading plate must be removedor the z-axis position of the top of the plate will change with theaddition of each new loading plate from a new package of pipette tips.

SUMMARY

Some embodiments of a pipette tip dispensing device, include adisplacement actuator having an actuator housing with a top portion,four sides, and an inner surface. The actuator housing also has aplurality of regularly spaced detent members disposed on at least oneside of the housing and a plurality of proximal alignment membersdisposed in a regularly spaced array on a top portion of the actuatorwith each proximal alignment member configured to releasably engage andrestrict lateral displacement of a proximal end of a pipette tip engagedtherewith. An alignment housing of the device includes an outsidesurface in contact with the inside surface of the displacement actuatorhousing in a sliding arrangement. A plurality of regularly spaced detentmembers are configured to releasably engage the detent members of theactuator housing. In addition, the detent members of the alignmenthousing have a regular spacing that is substantially the same as theregular spacing of the detent members of the actuator housing. Aproximal opening of the alignment housing has an inside surfaceconfigured to engage outer lateral sides of a loading block. A distalbarrier element is disposed at a top portion of the alignment housingand includes a plurality of restrictive apertures which aresubstantially aligned with corresponding proximal alignment members.

Some embodiments of a pipette tip dispensing device include adisplacement actuator having an actuator housing that includes an insidesurface, a clear thin rigid material formed into a substantiallyrectangular configuration with an open bottom portion, substantiallyplanar sides and a plurality of regularly spaced detent members disposedon at least one sides thereof. A proximal actuator plate (also referredto herein as an “activator plate”) of the actuator includes a pluralityof proximal alignment members disposed substantially in a plane in aregularly spaced array and each proximal alignment member configured toreleasably engage and restrict lateral displacement of a proximal end ofa pipette tip engaged therewith. An alignment housing assembly of thedevice includes a substantially rectangular structure having an outsidesurface configured to engage the inside surface of the actuator housing,four sides formed from a clear thin substantially rigid material with aplurality of regularly spaced detent members configured to releasablyengage the detent members of the actuator housing and having a regularspacing that is substantially the same as the regular spacing of thedetent members of the actuator housing. A proximal opening of thealignment housing is configured to engage an outside perimeter of aloading block. An outer surface of the alignment housing is configuredto slidingly engage an inner surface of the actuator housing so as toallow relative movement therebetween. A substantially planar distalbarrier element is disposed at a top portion of the alignment housingand has a plurality of restrictive apertures which are substantiallyaligned with respective proximal alignment members and which areconfigured to engage an outside surface of a pipette tip, restrictlateral displacement of a pipette tip and resist axial displacement ofthe pipette tip until an axial force threshold imparted to the pipettetip is reached. Once a threshold axial force is imparted to a pipettetip engaged by restrictive aperture, the pipette tip will pass throughthe restrictive aperture so as to be dispensed.

Some embodiments of a method of simultaneously dispensing an array ofmultiple pipette tips into a loading block, include providing adispensing device that includes an array of regularly spaced pipettetips and engaging the dispensing device with a loading block such thatdistal ends of pipette tips which are engaged with restrictive aperturesof a barrier member of the dispensing device are disposed withinreceptacles of the loading block. Thereafter, an actuator of thedispensing device is actuated so as to apply an axial force on the arrayof pipette tips engaged with the restrictive apertures of the dispensingdevice until a threshold axial force is applied and the array of pipettetips engaged with the restrictive apertures is dispensed into respectivereceptacles in the loading block.

In some embodiments, provided herein is a pipette tip dispensing device,comprising a displacement actuator which includes an actuator housinghaving a top portion, four sides, and an inner surface, a plurality ofregularly spaced detent members disposed on at least one side of thehousing, and a plurality of proximal alignment members disposed in aregularly spaced array on a top portion of the actuator with eachproximal alignment member configured to releasably engage and restrictlateral displacement of a proximal end of a pipette tip engagedtherewith. The device also comprises an alignment housing including anoutside surface in contact with the inside surface of the displacementactuator housing in a sliding arrangement, a plurality of regularlyspaced detent members configured to releasably engage the detent membersof the actuator housing and having a regular spacing that issubstantially the same as the regular spacing of the detent members ofthe actuator housing, and a proximal opening having an inside surfaceconfigured to engage outer lateral sides of a loading block 26. Thedevice also comprises a distal barrier element disposed at a top portionof the alignment housing having a plurality of restrictive apertureswhich are substantially aligned with corresponding proximal alignmentmembers.

In certain embodiments, the pipette tip dispensing device furthercomprises a plurality of pipette tips disposed in a nested, regularlyspaced array between the respective proximal alignment members andrestrictive apertures with a longitudinal axis of each nested set ofpipette tips being substantially aligned and coaxial with the respectiveproximal alignment members and restrictive apertures. The regularspacing of the restrictive apertures and proximal alignment members canbe about 9 mm. The proximal alignment members comprise cone shapedabutments extending from a distal surface of the proximal actuatorplate.

In some embodiments, a pipette tip dispensing device has actuatorhousing and alignment housing comprised of a polymer material. Thepolymer material of the actuator housing and alignment housing comprisesmolded polypropylene in some embodiments. The polymer material of theactuator housing and alignment housing comprises a thickness of about0.005 inches to about 0.05 inches in certain embodiments.

Provided also is a pipette tip dispensing device having an actuatorhousing comprised of a telescoping arrangement which has multiplehousing elements. The restrictive apertures of the barrier elementcomprise holes sized to mechanically engage a major outer transversedimension of a proximal portion of a pipette tip and prevent axialdisplacement of the proximal portion through the aperture until athreshold axial force is applied to the engaged pipette tip at whichtime the proximal portion is deflected and compressed to allow passagethrough the restrictive aperture.

In some embodiments, provided is a pipette tip dispensing device,comprising a displacement actuator comprising an actuator housing thatincludes an inside surface, a clear thin rigid material formed into asubstantially rectangular configuration with an open bottom portion,substantially planar sides and a plurality of regularly spaced detentmembers disposed on at least one sides thereof, and a proximal actuatorplate having a plurality of proximal alignment members disposedsubstantially in a plane in a regularly spaced array and each proximalalignment member configured to releasably engage and restrict lateraldisplacement of a proximal end of a pipette tip engaged therewith; analignment housing assembly including a substantially rectangularstructure having an outside surface configured to engage the insidesurface of the actuator housing, four sides formed from a clear thinsubstantially rigid material with a plurality of regularly spaced detentmembers configured to releasably engage the detent members of theactuator housing and having a regular spacing that is substantially thesame as the regular spacing of the detent members of the actuatorhousing, and a proximal opening configured to engage an outsideperimeter of a loading block, an outer surface configured to slidinglyengage an inner surface of the actuator housing so as to allow relativemovement there between; and a substantially planar distal barrierelement disposed at a top portion of the alignment housing having aplurality of restrictive apertures which are substantially aligned withrespective proximal alignment members and which are configured to engagean outside surface of a pipette tip, restrict lateral displacement of apipette tip and resist axial displacement of the pipette tip until anaxial force threshold imparted to the pipette tip is reached.

In certain embodiments, the pipette tip dispensing device furthercomprises a plurality of pipette tips disposed in a nested, regularlyspaced array between the respective proximal alignment members andrestrictive apertures with a longitudinal axis of each nested set ofpipette tips being substantially aligned and coaxial with the respectiveproximal alignment members and restrictive apertures. In thisembodiment, the pipette tip dispensing device can have restrictiveapertures and proximal alignment members having regular spacing about 9mm. The pipette tip dispensing device also can have proximal alignmentmembers comprising cone shaped abutments extending from a distal surfaceof the proximal actuator plate. The pipette tip dispensing device canhave an actuator housing and alignment housing comprising a polymermaterial. The polymer material of the actuator housing and alignmenthousing can comprise molded polypropylene. The polymer material of theactuator housing and alignment housing can comprise a thickness of about0.005 inches to about 0.05 inches. The actuator housing can alsocomprise a telescoping arrangement having multiple housing elements. Therestrictive apertures of the barrier element can also comprise holessized to mechanically engage a major outer transverse dimension of aproximal portion of a pipette tip and prevent axial displacement of theproximal portion through the aperture until a threshold axial force isapplied to the engaged pipette tip at which time the proximal portion isdeflected and compressed to allow passage through the restrictiveaperture.

Also provided is a method of simultaneously dispensing an array ofmultiple pipette tips into a loading block, which comprises providing adispensing device that includes an array of regularly spaced pipettetips; engaging the dispensing device with a loading block such thatdistal ends of pipette tips which are engaged with restrictive aperturesof a barrier member of the dispensing device are disposed withinreceptacles of the loading block; actuating an actuator of thedispensing device so as to apply an axial force on the array of pipettetips engaged with the restrictive apertures of the dispensing device toovercome a threshold axial force and eject the array of pipette tipsengaged with the restrictive apertures into respective receptacles inthe loading block.

In some embodiments, the dispensing device further comprises a pluralityof pipette tips disposed in a nested, regularly spaced array betweenrespective proximal alignment members and restrictive apertures with alongitudinal axis of each nested set of pipette tips being substantiallyaligned and coaxial with the respective proximal alignment members andrestrictive apertures and further comprising multiple actuations of theactuator in order to eject a plurality of arrays of multiple pipettetips.

In certain embodiments, the actuator further comprises a plurality ofregularly spaced proximal alignment members configured as cone shapedabutments extending from a distal surface of a proximal actuator plate,the barrier member comprises a barrier plate and where actuating theactuator comprises moving the proximal actuator plate towards thebarrier plate with threshold axial force sufficient to force an array ofpipette tips through the restrictive apertures of the barrier plate.

In some embodiments, the actuator housing and alignment housing comprisea clear polymer material and further comprising visualizing the ejectionof the array of multiple pipette tips from the restrictive apertures ofthe barrier member during actuation. The actuator housing can comprise atelescoping arrangement having multiple housing elements and whereactuation of the actuator comprises collapsing the multiple housingelements from an extended state to a collapsed nested state. Therestrictive apertures of the barrier element can comprise holes sized tomechanically engage a major outer transverse dimension of a proximalportion of a pipette tip and prevent axial displacement of the proximalportion through the aperture until a threshold axial force is applied tothe engaged pipette tip and further comprising actuating the actuatoruntil the proximal portion of each pipette tip of the array of multiplepipette tips engaged with the restrictive apertures are deflected andcompressed to allow passage through the restrictive apertures andbarrier member.

Provided in some embodiments is a pipette tip dispensing device,comprise (a) a housing; (b) a distal barrier plate in effectiveconnection with the housing; and (c) a plurality of nested pipette tipunits where each unit is aligned with a channel in the distal barrierplate, and where the distal barrier plate comprises (i) a plurality ofchannels, where each channel has a diameter larger than the widestportion of a pipette tip; (ii) a top surface, and (iii) a bottom surfacethat comprises a plurality of tails around some or all of the channels,where: (1) the tails extend in a nearly perpendicular orientation fromthe bottom surface, and (2) the tails around each channel contact apipette tip when a pipette tip is dispensed and passes by the tails,thereby imparting (e.g., applying) a frictional force on the pipette tipwhen it is dispensed. In some embodiments, the tails deflect outwardsagainst the pipette tip before, and/or at the same time the pipette tipis being dispensed (e.g., the pipette tip is translating), and sometimesthe tails contact the proximal portion of a pipette tip. In someembodiments, a subset of channels in the distal barrier plate aresurrounded by tails that eject pipette tips of an array at one time, andanother subset of channels in the plate are surrounded by tails thateject pipette tips of the same array at another time. A distal barrierplate may include 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16,17, 18, 19 or 20 of such subsets of channels.

In some embodiments pertaining to a dispensing device described in thepreceding paragraph, the top surface and/or the bottom surface issubstantial flat or planar. In certain embodiments, each channel in thedispensing device can comprise 2, 3, 4, 5, 6, 7, 8, 9, 10 or more tails.Each channel of the barrier plate can comprise tails of the same length.In some embodiments, each channel of the barrier plate can comprisetails of different lengths in some embodiments. Channels located in thecenter of the barrier plate can comprise the longest tails. In certainembodiments, channels located in the center of the barrier plate cancomprise the shortest tails. Subsequent channels concentrically disposedabout a central longitudinal axis can comprise sequentially shortertails in length in a stepwise manner in some embodiments. In certainembodiments, subsequent channels concentrically disposed about a centrallongitudinal axis can comprise sequentially longer tails in length in astepwise manner. Channels located in the center of the barrier platealong the X axis can comprise tails of the same length and channelsalong the Y axis comprise tails of varying length in some embodiments.Channels located in the center of the barrier plate along the Y axis cancomprise tails of the same length and channels along the X axis comprisetails of varying length in certain embodiments. Channels located in thecenter of the barrier plate along the X and Y axes can comprise tails ofvarying length in some embodiments. Each channel can comprise an evennumber of tails in certain embodiments. Tails directly opposite oneanother around a channel can have the same length, and in someembodiments, tails directly opposite one another around a channel canhave a different length. Tails adjacent to one another can have adifferent length in certain embodiments. The tails can be at an internalangle of about 89° to about 80° from the bottom surface of the distalbarrier plate in some embodiments. The tails can be at an internal anglebetween 88-85°, 87-84°, 86-83° or 86-85° from the bottom surface of thedistal barrier plate in some embodiments. The tails can be at aninternal angle of about 87° from the bottom surface of the distalbarrier plate in certain embodiments, and tails sometimes can be between0.01 μm-2.0 mm in length. The tails can be between 0.05 μm-2.0 mm inlength in certain embodiments. The tails around a channel are not in thechannel in some embodiments. In certain embodiments, the housing cancomprise (a) an actuator housing comprising a top portion, four sides,an inner surface, and a plurality of regularly spaced detent membersdisposed on at least one side of the housing, and (b) an alignmenthousing comprising an outside surface in contact with the inside surfaceof the actuator housing in a sliding arrangement, a plurality ofregularly spaced detent members configured to releasably engage thedetent members of the actuator housing and having a regular spacing thatis substantially the same as the regular spacing of the detent membersof the actuator housing, and a proximal opening having an inside surfaceconfigured to engage outer lateral sides of a loading block in certainembodiments. The housing can comprise a polymer material, and thepolymer material of the housing can comprise molded polypropylene insome embodiments. The polymer material of the housing can comprise athickness of about 0.005 inches to about 0.05 inches. The actuatorhousing can comprise a telescoping arrangement having multiple housingelements. The alignment housing can comprise a flange or a footing forthe housing to rest in some embodiments. The actuator housing cancomprise a member on the top portion of the actuator that maintainscontact with and restricts lateral displacement of the proximal portionof the pipette tips in certain embodiments, where the member can beselected from the group consisting of foam, a raised grid, and aplurality of proximal alignment members in some embodiments. The devicecan comprise one or more arrays of 96, 384, 1356 or more pipette tips. Apipette tip unit can be arranged in an array of pipette tip units, andeach pipette tip unit can comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,13, 14 or more nested pipette tips in some embodiments.

Also provided in some embodiments is a distal barrier plate that can bepart of a pipette tip dispenser and is not in association with pipettetips, that comprises (a) a plurality of channels, where each channelcomprises a diameter larger than the widest portion of a pipette tip;(b) a top surface; and (c) a bottom surface that comprises a pluralityof tails around some or all of the channels, where: (i) the tails extendin a nearly perpendicular orientation from the bottom surface, and (ii)the tails around each channel contact a pipette tip when a pipette tipis dispensed and passes by the tails, thereby applying a frictionalforce on the pipette tip when it is dispensed. In some embodiments, thetails deflect outwards against the pipette tip before the pipette tip isdispensed, and/or at the same time the pipette tip is being dispensed(e.g., the pipette tip is translating), and sometimes the tails contactthe proximal portion of a pipette tip. In some embodiments, a subset ofchannels in the distal barrier plate are surrounded by tails that ejectpipette tips of an array at one time, and another subset of channels inthe plate are surrounded by tails that eject pipette tips of the samearray at another time. A distal barrier plate may include 2, 3, 4, 5, 6,7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 of such subsets ofchannels.

In some embodiments pertaining to a dispensing devices described in thepreceding paragraph, the top surface and/or the bottom surface issubstantial flat or planar. In certain embodiments, each channel cancomprises 2, 3, 4, 5, 6, 7, 8, 9, 10 or more tails. Each channel of thebarrier plate can comprise tails of the same length, and in someembodiments each channel of the barrier plate can comprise tails ofdifferent lengths. Channels located in the center of the barrier platecan comprise the longest tails. In certain embodiments, channels locatedin the center of the barrier plate can comprise the shortest tails.Subsequent channels concentrically disposed about a central longitudinalaxis can comprise sequentially shorter tails in length in a stepwisemanner. In certain embodiments, subsequent channels concentricallydisposed about a central longitudinal axis can comprise sequentiallylonger tails in length in a stepwise manner. Channels located in thecenter of the barrier plate along the X axis can comprise tails of thesame length and channels along the Y axis can comprise tails of varyinglength in certain embodiments. In some embodiments, channels located inthe center of the barrier plate along the Y axis can comprise tails ofthe same length and channels along the X axis can comprise tails ofvarying length. Channels located in the center of the barrier platealong the X and Y axes can comprise tails of varying length in someembodiments. Each channel can comprise an even number of tails. Tailsdirectly opposite one another around a channel can have the same lengthin some embodiments. In certain embodiments, tails directly opposite oneanother around a channel can have a different length. Tails adjacent toone another can have a different length in some embodiments. In certainembodiments, tails are at an internal angle of about 89° to about 80°from the bottom surface of the distal barrier plate. The tails can be atan internal angle between 88-850, 87-84°, 86-83° or 86-85° from thebottom surface of the distal barrier plate in some embodiments. Incertain embodiments, the tails can be at an internal angle of about 87°from the bottom surface of the distal barrier plate. The tails can bebetween 0.01 μm-2.0 mm in length, and sometimes the tails can be between0.05 μm-2.0 mm in length. The tails around a channel are not in thechannel in some embodiments.

Provided also in some embodiments is a method for simultaneouslydispensing an array of pipette tips into a loading block, whichcomprises (a) providing a dispensing device that includes an array ofregularly spaced pipette tips; (b) engaging the dispensing device with aloading block such that distal ends of pipette tips are disposed aboveor within receptacles of the loading block, the barrier plate comprising(i) a plurality of channels, where each channel has a diameter largerthan the widest portion of a pipette tip; (ii) a top surface; and (iii)a bottom surface that comprises a plurality of tails around some or allof the channels, where the tails extend in a nearly perpendicularorientation from the bottom surface; and (c) actuating an actuator ofthe dispensing device so as to apply an axial force on the array ofpipette tips, where the axial force dispenses the array of pipette tipsthrough the channels and past the tails, whereby the tails contact thepipette tips and impart a frictional force on the pipette tips, therebyejecting the array of pipette tips into respective receptacles in theloading block. In some embodiments, the tails deflect outwards againstthe pipette tip before the pipette tip is dispensed, and/or at the sametime the pipette tip is being dispensed (e.g., the pipette tip istranslating), and sometimes the tails contact the proximal portion of apipette tip. In some embodiments, a subset of channels in the distalbarrier plate are surrounded by tails that eject pipette tips of anarray at one time, and another subset of channels in the plate aresurrounded by tails that eject pipette tips of the same array at anothertime. A distal barrier plate may include 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,12, 13, 14, 15, 16, 17, 18, 19 or 20 of such subsets of channels.

In some embodiments pertaining to a dispensing device described in thepreceding paragraph, the top surface and/or the bottom surface issubstantial flat or planar. In certain embodiments, the barrier platecan comprise 2, 3, 4, 5, 6, 7, 8, 9, 10 or more tails. Each channel ofthe barrier plate can comprise tails of the same length. In someembodiments, each channel of the barrier plate can comprise tails ofdifferent lengths. Channels located in the center of the barrier platecan comprise the longest tails. In some embodiments, channels located inthe center of the barrier plate can comprise the shortest tails.Subsequent channels concentrically disposed about a central longitudinalaxis can comprise sequentially shorter tails in length in a stepwisemanner in some embodiments. Subsequent channels concentrically disposedabout a central longitudinal axis can comprise sequentially longer tailsin length in a stepwise manner in certain embodiments. In someembodiments, channels located in the center of the barrier plate alongthe X axis can comprise tails of the same length and channels along theY axis comprise tails of varying length. In some embodiments, channelslocated in the center of the barrier plate along the Y axis can comprisetails of the same length and channels along the X axis comprise tails ofvarying length. In certain embodiments, channels located in the centerof the barrier plate along the X and Y axes can comprise tails ofvarying length. Each channel can comprise an even number of tails insome embodiments, and in certain embodiments tails directly opposite oneanother around a channel can have the same length. Tails directlyopposite one another around a channel can have a different length insome embodiments, and in certain embodiments, tails adjacent to oneanother can have a different length. The tails can be at an internalangle of about 89° to about 80° from the bottom surface of the distalbarrier plate in some embodiments. In certain embodiments, tails can beat an internal angle between 88-85°, 87-84°, 86-83° or 86-85° from thebottom surface of the distal barrier plate. In some embodiments, tailscan be at an internal angle of about 87° from the bottom surface of thedistal barrier plate. The tails can be between 0.01 μm-2.0 mm in lengthin some embodiments, and in certain embodiments, the tails can bebetween 0.05 μm-2.0 mm in length. The tails around a channel are not inthe channel in some embodiments. The actuator can comprise an actuatorhousing and an alignment housing both having a clear polymer material tovisualize ejection of the array of multiple pipette tips from the tailsof the barrier member during actuation in some embodiments. The actuatorhousing can comprise a telescoping arrangement having multiple housingelements and where actuation of the actuator comprises collapsing themultiple housing elements from an extended state to a collapsed nestedstate in certain embodiments.

Certain embodiments are described in the following detailed description,claims and drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

The drawings illustrate embodiments of the invention and are notlimiting. For clarity and ease of illustration, the drawings are notmade to scale and, in some instances, various aspects may be shownexaggerated or enlarged to facilitate an understanding of particularembodiments.

FIG. 1 shows an exploded perspective view of an embodiment of a pipettetip dispensing device.

FIG. 2 shows an elevation view of an embodiment of a pipette tip.

FIG. 3 illustrates a cross section of the pipette tip of FIG. 2 takenalong lines 3-3 of FIG. 2.

FIG. 4 shows a perspective view of the pipette tip dispensing device ofFIG. 1.

FIG. 5A is a transverse cross section of the dispensing device of FIG. 4taken along lines 5A-5A of FIG. 4, showing a single column of threenested pipette tips disposed between a proximal alignment member of theactuator plate and a respective restrictive aperture of the barrierplate.

FIG. 5B shows the view of FIG. 5A after the actuator has been fullyactuated three clicks to a position where all nested pipette tips havebeen ejected into loading blocks and the proximal alignment members aredisposed within respective distal restrictive apertures.

FIG. 6A shows an enlarged cut-away view in partial section of a stackednested array of pipette tips engaged with a proximal alignment member,distal restrictive aperture and loading block prior to actuation.

FIG. 6B shows the same view as FIG. 6A after the actuator has beenadvanced or actuated one click so as to move the actuator plate towardsthe barrier plate and eject the distal most pipette tip of the nestedcolumn into the corresponding aperture of the loading block.

FIG. 7 shows an elevation view of an embodiment of a pipettor with apipette tip engaged with a distal nozzle thereof.

FIG. 8 is a perspective view of an embodiment of a loading block.

FIG. 9 shows a distal nozzle of a pipettor engaging a proximal port of apipette tip disposed in a loading block.

FIG. 10 shows multiple nozzles of an automated manifold engagingmultiple corresponding pipette tips disposed in a loading block.

FIG. 11 shows an elevation view in transverse cross section of atelescoping embodiment of a pipette tip dispensing device with theactuator housing assembly in a fully extended state and a full column ofnested pipette tips disposed between the barrier plate and proximalalignment members.

FIG. 12 shows the pipette tip dispensing device of FIG. 11 in acompressed state with the telescoping elements of the actuator housingin a collapsed state.

FIG. 13A shows a perspective view of a distal barrier plate with tailspointing in an upward orientation.

FIG. 13B shows an enlarged cut away view of FIG. 13A (see arrows in FIG.13A) detailing the tails.

FIG. 13C shows a lateral partial profile view of the tails, where allthe tails are the same length. FIG. 13D shows an enlarged cut away,lateral partial profile view of one channel, where the orientation ofthe each tail is in part defined by an internal angle theta.

FIG. 14A shows a bottom view of a distal barrier plate with tailsarranged in a nearly perpendicular orientation with respect to thebottom surface of the plate. FIG. 14A shows X and Y axes referencedherein.

FIG. 14B shows an enlarged cut away view of FIG. 14A (see arrows in FIG.14A) detailing certain aspects of tails and their orientation tochannels.

FIG. 14C shows a lateral profile view of the tails, where the tails arevaried in length.

DETAILED DESCRIPTION

Discussed herein are method and device embodiments for handling, storageand dispensing of pipette tips used for a variety of material handlingapplications. Pipette tips may generally be engaged with a distal nozzleof a pipettor or similar device in order to draw and drop liquid slugsin precise amounts. Such tips may be used for the transfer and handlingof liquids for applications such as titration and dispensing of liquids,DNA sequencing, cycle sequencing, PCR and other DNA analysis as well asother liquid handling applications. For many of these applications,large numbers of samples must be processed in a precise manner and, assuch, a large number of pipette tips are used for such methods. In orderto avoid cross contamination of samples, pipette tips are typically usedonly once for each sample being processed. Because of the large numberof samples being processed and the single use nature of the pipettetips, a large number of pipette tips need to engaged with pipettor typedevices and then removed from those devices and disposed of.

Due to such large volume handling and disposal, it is desirable for someapplications to have devices and methods for pipette tip transfer andloading in arrays of multiple tips from a single packaging source toavoid the need for disposing of a package for each array loaded onto apipettor device. What is also desirable for some applications aredevices and methods for loading an array of multiple pipette tipswithout the need to transfer a separate loading plate from the packagingof the tips which may cause additional waste for disposal in addition toaffecting the cumulative z-axis height of the pipette tips being loaded.Some pipette tip dispensing device and method embodiments discussedherein are directed to the handling, storage and simultaneous dispensingof a plurality of pipette tips disposed in a regularly spaced array intoa loading plate or block. Some of these embodiments have the capacity toserially dispense multiple arrays or pipette tips without transferringloading plates or the need for handling of individual pipette tips. Someembodiments of pipette tip dispensing devices discussed herein are alsocapable of dispensing arrays of multiple pipette tips accurately andconveniently without the need to transfer a loading tray from thepackaging of the pipette tips.

Device and method embodiments described herein provide severaladvantages. Device and method embodiments herein allow for storing,loading or handling of pipette tips, and allow for convenient loading ofpipette tips without the need to transfer a storage plate that mayaffect the z-axis location of the top surface of the loading block intowhich the pipette tips are transferred. Device and method embodimentsherein also allow for multiple pipette tips to be loaded simultaneouslywithout the transfer of a storage plate. Such embodiments also allow forpipette tips to be stored in a nested configuration, in one or morenested column arrays for some embodiments, and allow the bottom pipettetip of each nested column to be conveniently dispensed into a loadingplate or loading block.

A pipette tip can be of any geometry useful for dispensing fluids incombination with a dispensing device. Pipette tips sometimes areavailable in sizes that hold from 0 to 10 microliters, 0 to 20microliters, 1 to 100 microliters, 1 to 200 microliters and from 1 to1000 microliters, for example. The external appearance of pipette tipsmay differ, and certain pipette tips can have a continuous tapered wallforming a central channel or tube that is roughly circular in horizontalcross section, in some embodiments. A pipette tip can have anycross-sectional geometry that results in a tip that (i) providessuitable flow characteristics, and (ii) can be fitted to a dispenser(e.g., pipette), for example. Pipette tips sometimes taper from thewidest point at the top-most portion of the pipette tip (pipetteproximal end or end that engages a dispenser), to a narrow opening atthe bottom most portion of the pipette tip (pipette distal end or endused to acquire or dispel fluid). In certain embodiments, a pipette tipwall includes two or more taper angles. The inner surface of the pipettetip sometimes forms a tapered continuous wall, in some embodiments, andin certain embodiments, the external wall may assume an appearanceranging from a continuous taper to a stepped taper or a combination ofsmooth taper with external protrusions. An advantage of an externallystepped taper is compatibility with pipette tip racks from differentmanufacturers. The bore of the top-most portion of the central channelor tube generally is wide enough to accept a particular dispenserapparatus (e.g., nozzle, barrel).

In some embodiments, a pipette tip has (i) an overall length of about1.10 inches to about 3.50 inches (e.g., about 1.25, 1.50, 1.75, 2.00,2.25, 2.50, 2.75, 3.00, 3.25 inches); (ii) a fluid-emitting distalsection terminus having an inner diameter of about 0.01 inches to about0.03 inches (e.g., about 0.015, 0.020, 0.025 inches) and an outerdiameter of about 0.02 to about 0.7 inches (e.g., about 0.025, 0.03,0.04, 0.05, 0.06 inches); and (iii) a dispenser-engaging proximalsection terminus having an inner diameter of about 0.10 inches to about0.40 inches (e.g., about 0.15, 0.20, 0.25, 0.30, 0.35 inches) and anouter diameter of about 0.15 to about 0.45 inches (e.g., about 0.20,0.25, 0.30, 0.35, 0.45 inches). In the latter embodiments, the innerdiameter is less than the outer diameter.

The wall of the distal section of a pipette tip sometimes iscontinuously tapered from the wider portion, which is in effectiveconnection with the proximal section, to a narrower terminus. The wallof the distal section, in some embodiments, forms a stepped taperedsurface. The angle of each taper in a distal section is between aboutzero degrees to about thirty degrees from the central longitudinalvertical axis of the pipette tip (e.g., about 0, 1, 2, 3, 4, 5, 6, 7, 8,9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26,27, 28, 29 or 30 degrees), in certain embodiments. In some embodiments,the wall of the distal section forms stepped vertical sections. The wallthickness of a distal section may be constant along the length of thesection, or may vary with the length of the section (e.g., the wall ofthe distal section closer to the proximal section of the pipette tip maybe thicker or thinner than the wall closer to the distal sectionterminus; the thickness may continuously thicken of thin over the lengthof the wall). The distal section of a pipette tip generally terminatesin an aperture through which fluid passes into or out of the distalportion. A distal section of a pipette tip may contain a filter, insertor other material.

The wall of the proximal section of a pipette tip sometimes iscontinuously tapered from the top portion, a narrower terminus. The topportion generally is open and often is shaped to receive a pipette tipengagement portion of a dispensing device. The wall of a proximalsection, in some embodiments, forms a stepped tapered surface. The angleof each taper in the proximal section is between about zero degrees toabout thirty degrees from the central longitudinal vertical axis of thepipette tip (e.g., about 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13,14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30degrees), in certain embodiments. The wall thickness of a proximalsection may be constant over the length of the section, or may vary withthe length of the proximal section (e.g., the wall of the proximalsection closer to the distal section of the pipette tip may be thickeror thinner than the wall closer to the top of the proximal section; thethickness may continuously thicken or thin over the length of the wall).A proximal section of a pipette tip may contain a filter, insert orother material.

In certain embodiments, pipette tips in a pipette tray comprise one ormore of a filter component and/or an insert component. A filter may belocated in any suitable portion of a pipette tip, and sometimes islocated in a proximal portion of a pipette tip near a pipette tipaperture that can engage a dispensing device. A filter can be of anyshape (e.g., plug, disk; U.S. Pat. Nos. 5,156,811 and 7,335,337) and canbe manufactured from any material that impedes or blocks migration ofaerosol through the pipette tip to the proximal section terminus,including without limitation, polyester, cork, plastic, silica, gels,and the like, and combinations thereof. In some embodiments a filter maybe porous, non-porous, hydrophobic, hydrophilic or a combinationthereof. A filter in some embodiments may include vertically orientedpores, and the pore size may be regular or irregular. Pores of a filtermay include a material (e.g., granular material) that can expand andplug pores when contacted with aerosol (e.g., U.S. Pat. No. 5,156,811).In certain embodiments, a filter may include nominal, average or meanpore sizes of about 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, 0.5, or 0.05micrometers, for example. A section of a pipette tip also may include aninsert or material that can interact with a molecule of interest, suchas a biomolecule. The insert or material may be located in any suitablelocation for interaction with a molecule of interest, and sometimes islocated in the distal section of a pipette tip (e.g., a material or aterminus of an insert may be located at or near the terminal aperture ofthe distal section). An insert may comprises one or more components thatinclude, without limitation, multicapillaries (e.g., US 2007/0017870),fibers (e.g., randomly oriented or stacked, parallel orientation), andbeads (e.g., silica gel, glass (e.g. controlled-pore glass (CPG)),nylon, Sephadex®, Sepharose®, cellulose, a metal surface (e.g. steel,gold, silver, aluminum, silicon and copper), a magnetic material, aplastic material (e.g., polyethylene, polypropylene, polyamide,polyester, polyvinylidenedifluoride (PVDF)), Wang resin, Merrifieldresin or Dynabeads®). Beads may be sintered (e.g., sintered glass beads)or may be free (e.g., between one or two barriers (e.g., filter, frit)).Each insert may be coated or derivitized (e.g., covalently ornon-covalently modified) with a molecule that can interact with (e.g.,bind to) a molecule of interest (e.g., C18, nickel, affinity substrate).

FIG. 1 shows an exploded perspective view of an embodiment of a pipettetip dispensing device 10. The dispensing device embodiment 10 includes adisplacement actuator that has an actuator housing 12 with a topportion, four sides, and an inner surface. Sets of regularly spaceddetent members 14 are disposed on all four sides of the housing 12. Eachset of detent members 14 on the actuator housing 12 includes threedetent members 14 equally spaced in a vertical direction. A plurality ofproximal alignment members 16 are disposed in a regularly spaced arrayof 8×12 alignment members 16 on an actuator plate 18 disposed at a topportion of the actuator housing 12. Each proximal alignment member 16 isconfigured to releasably engage and restrict the lateral displacement ofa proximal end of a pipette tip, such as the pipette tip 20 illustratedin FIGS. 2 and 3.

An alignment housing 22 which is configured to slide within the actuatorhousing 12 includes an outside surface in contact with the insidesurface of the actuator housing 12 in a sliding arrangement. Thealignment housing 22 also includes a plurality of regularly spaceddetent members 24 which are configured to releasably engage thecorresponding detent members 14 of the actuator housing 12. As such, thedetent members 24 of the alignment housing have a regular spacing thatis substantially the same as the regular spacing of the detent members14 of the actuator housing as shown by arrow 15 in FIG. 5A. Also, thedetent members 24 of the alignment housing 22 have a shape that isconfigured to releasably engage the detent members 14 of the actuatorhousing. The alignment housing 22 has a rectangular proximal openingwith an inside surface which is sized and configured to engage outerlateral sides of a loading block 26 which is shown disposed within theproximal opening of the alignment housing 22.

A distal barrier element in the form of a distal barrier plate 28 isdisposed at a top portion of the alignment housing 22 and liessubstantially parallel to the actuator plate 18 of the actuator. Thedistal barrier plate 28 includes a plurality of restrictive apertures 32which are substantially aligned with corresponding respective proximalalignment members 16 of the actuator plate 18 within the actuatorhousing 12. The actuator housing 12 is configured to slide relative tothe alignment housing 22 to a collapsed state where the proximalalignment members 16 directly engage the restrictive apertures 32 of thedistal barrier plate 28 so as to push the last of a set of nestedpipette tips through the barrier plate and into the respective channels34 of the loading block 26 which is disposed below the barrier plate.

In FIG. 1, a single column of nested pipette tips is shown disposedbetween a proximal alignment member 16 and distal restrictive aperture32 for purposes of illustration, however, a column of nested pipettetips may generally be disposed between each proximal alignment member 16and corresponding restrictive aperture 32. The longitudinal axis 36 ofeach of the pipette tips 20 in the nested array are substantiallyaligned and coaxial as shown in FIG. 6A. A shoulder portion 38 of theproximal most pipette tip is disposed against a proximal end of theadjacent pipette tip. During typical use, a column of an equal number ofnested pipette tips 20 may be disposed between each of the respectiveproximal alignment members 16 and distal restrictive apertures 32 in aconfiguration that is the same as or similar to the configuration ofnested tips shown. In addition, any desired number of columns could beused. The regular spacing of the proximal alignment members 16, distalrestrictive apertures 32, and columns of nested pipette tips disposedtherebetween may be about 1 mm to about 5 mm for some embodiments.

A specific embodiment of pipette tip 20 is shown in FIGS. 2 and 3,however, pipette tips may have a wide variety of configurations,dimensions and materials, each of which may be accommodated for use withany of the dispensing device embodiments discussed herein. For example,pipette tips may be configured as filter tips that include one, two,three or more filter elements disposed within a barrel of the tip inorder to block aerosols from the pipettor device as well as otherpurposes.

The pipette tip 20 shown has a generally barrel shaped configurationwhich is concentrically disposed about a longitudinal axis 36 of thepipette tip 20. An inner lumen 40 extends coaxially along the length ofthe pipette tip 20 and tapers generally from the proximal opening of thepipette tip to a smaller distal opening. The proximal opening at aproximal end 42 of the tip 20 may have an inside surface with a taperedcontour that is configured to engage an outer surface of a distal nozzleof a pipettor device, such as the pipettor device 44 shown in FIG. 7, ina sealed and releasable arrangement.

An outer surface of the proximal end of the pipette tip may have a rim,shoulder or other structure 46 that forms a major outer transversedimension of the tip 20 which is disposed at the axial position of thepipette tip 20 having the largest transverse dimension. The barrelshaped configuration may have a generally round transverse cross sectionwith the major outer transverse dimension at the proximal end 42 of thepipette tip of about 0.2 inches to about 0.4 inches, more specifically,about 0.25 inches to about 0.35 inches, for some embodiments. The outertransverse dimension of the pipette tip may taper to a minor outertransverse dimension at a distal end of the pipette tip 20 of about 0.02inches to about 0.05 inches, more specifically, about 0.03 inches toabout 0.04 inches, for some embodiments. The inner lumen may have acontour and taper that substantially corresponds to the taper andcontour profile of the outer surface. The distal port or opening at thedistal end of the inner lumen of the pipette tip may have a transversedimension or diameter of about 0.01 inches to about 0.03 inches, morespecifically, about 0.015 inches to about 0.025 inches, for someembodiments.

The shoulder portions 38 of the outer surface of some pipette tipembodiments 20 may have a minor transverse dimension that will fitwithin the proximal opening of another similar pipette tip and a majortransverse dimension that is larger than the proximal opening of asimilar pipette tip. With such an arrangement, the shoulder portion 38of a first pipette tip thereby includes a distal surface or feature thatmay engage a proximal end or surface of another corresponding secondpipette tip that is in nested engagement with the first pipette tip. Theengagement of the shoulder portion of the first pipette tip with aproximal surface of the second pipette tip allows the transfer axialforce between the first and second nested pipette tips without engagingthe respective inner and outer tapered surfaces of the tips which mightcause them to bind together making release of the tips from each otherdifficult.

The wall thickness of some embodiments of pipette tips may be about0.003 inches to about 0.01 inches and the overall length of some pipettetip embodiments may be about 1.5 inches to about 3.5 inches, morespecifically, about 2 inches to about 3 inches. Some embodiments ofpipette tips may be made of suitable polymers such as polypropylene,polyethylene, polystyrene, polyurethane and the like as well as anyother suitable polymers. Such polymer materials as well as others may beconfigured to allow the proximal end or portion of the pipette tip toelastically deform or compress sufficiently to allow passage through therestrictive aperture 32 of the barrier member 28 if sufficient thresholdaxial force is applied to a pipette tip 20 engaged with a restrictiveaperture 32. For such embodiments, once the pipette tip 20 has passedthrough the restrictive aperture 32, and the inward radial constraint ofthe restrictive aperture on the pipette tip has been removed, theproximal end or portion elastically returns to its original shape. Sucha process may occur with any structure 46 that forms the major outertransverse dimension of the pipette tip 20.

Referring again to FIG. 1 as well as FIGS. 4-6, the pipette tipdispensing device 10 is shown in more detail. The displacement actuatorincludes the actuator housing 12 that may be made from a clear, thinrigid material formed into a substantially rectangular configurationwith an open bottom portion, substantially planar sides that may bearranged substantially perpendicular to each other and to the topsurface and actuator plate 18 disposed within an upper end of thehousing 12. For some embodiments, the actuator housing 12 may be madefrom a thin clear polymer material that is transparent or translucentand may have a thickness of about 0.005 inches to about 0.05 inches. Forsome embodiments, the actuator housing 12 may be made from suitablemetals, such as aluminum, or polymers such as polypropylene,polycarbonate, polyethylene, polystyrene, polyurethane and the like aswell as any other suitable polymers that may be molded, thermoformed orthe like. The housing 12 may have a thickness that allows for someflexibility or elastic deformation of the sides or proximal surface uponmanual manipulation but provides sufficient structural strength tomaintain its general shape upon manual manipulation and actuation. Theactuator housing 12 is also sufficiently rigid to be self-supporting andmaintains integrity sufficient to apply actuation force on the actuatorplate 18 and the array of pipette tips 20 being dispensed through therestrictive apertures 32 of the barrier plate 28.

The proximal actuator plate 18 has a plurality of proximal alignmentmembers 16 disposed substantially in a plane in a regularly spaced arrayand each proximal alignment member 16 is configured to releasably engageand restrict lateral displacement of a proximal end of a pipette tip 20that is engaged with the alignment member 16. The proximal alignmentmembers 16 may be cone shaped abutments extending from a distal surfaceof the actuator plate 18 that may be configured to engage or fit withinthe proximal port of corresponding pipette tips to be used with theproximal actuator plate 18. The proximal actuator plate 18 may be madefrom suitable metals, such as aluminum, or polymers such aspolypropylene, polycarbonate, polyethylene, polystyrene, polyurethaneand the like as well as any other suitable polymers that may be molded,thermoformed or the like. The proximal actuator plate 18 and proximalalignment members 16 may be molded from a monolithic structure of thesame material for some embodiments. The proximal actuator plate 18 mayhave a thickness of about 0.05 inches and about 0.25 inches. Theproximal actuator plate 18 may be secured to an inner proximal surfaceof the actuator housing and may be configured with sufficient rigidityto maintain a generally planar configuration when applying axial forceto an array of pipette tips 20 engaged with the proximal members 16thereof as the pipette tips are being pushed through the restrictiveapertures 32 of the distal barrier plate 28. For some embodiments, theproximal actuator plate may be integrally molded or otherwise formedwith the actuator housing 12. Some pipette tip array embodiments of theactuator plate 18 and barrier member may include 96 pipette tip arraysof 8×12 pipette tips spaced about 9 mm apart center to center, someother embodiments may include 384 pipette tip arrays of 16×24 pipettetips spaced about 4.5 mm apart center to center. Other pipette tip arrayembodiments may include more or less pipettes depending on theapplication.

The alignment housing assembly includes a substantially rectangularstructure having an outside surface which is configured to slidinglyengage the inside surface of the actuator housing 12. The alignmenthousing embodiment 22 shown has four sides formed from a clear, thin,substantially rigid material that may be transparent or translucent inorder to allow an operator to visualize a pipette tip loading process.The four sides of the alignment housing 22 include the regularly spaceddetent members 24 which are configured to releasably engage thecorresponding detent members 14 of the actuator housing 12. The detentmembers 24 have a regular vertical spacing that is substantially thesame as the regular vertical spacing of the detent members of theactuator housing. The engagement of corresponding detent members securesthe actuator housing 12 in fixed relation to the alignment housing untila threshold force applied to one of the housings relative to the otherovercomes the detent engagement. The detent engagement may be used tofacilitate incremental movement between the housings while maintainingthe housings in a mechanically coupled relation when not in use, duringshipment while loaded with nested arrays of pipette tips or at any othersuitable time. The amount of engagement of the corresponding detentmembers may be about 0.005 inches to about 0.05 inches for someembodiments. The angle that the sides of the alignment housing 22 formwith the barrier plate 28 may be the same as or similar to the angle thesides of the actuator housing 12 form with the actuator plate 18. Thesesimilar angles may be configured to facilitate the sliding ortelescoping movement between the inside surface of the sides of theactuator housing 12 and the outer surface of the sides of the alignmenthousing 22.

The alignment housing 22 may be made from the same thin clear polymermaterial as that of the actuator housing 12 and have a similardimensional configuration such as a thickness of about 0.005 inches toabout 0.05 inches. For some embodiments, the alignment housing may bemade from suitable metals, such as aluminum, or polymers such aspolypropylene, polycarbonate, polyethylene, polystyrene, polyurethaneand the like as well as any other suitable polymers that may be molded,thermoformed or the like. The alignment housing 22 may have a thicknessthat allows for some flexibility or elastic deformation of the sides orproximal surface upon manual manipulation but provides sufficientstructural strength to maintain its general shape upon manualmanipulation and actuation and may be self-supporting. In particular,the alignment housing 22 maintains integrity sufficient to resistactuation force on an array of pipette tips being dispensed through therestrictive barrier plate 28 at the top or proximal end of the alignmenthousing 22.

The alignment housing 22 includes a proximal opening 48 which has aninside surface or flange that is configured to engage an outside surfaceperimeter of the loading block 26. For some embodiments, the proximalopening 48 of the alignment housing may be covered with a thin material,such as a thin polymer material (not shown) for storage and shipment ofthe device. Such a cover material may be configured to be temporarilysecured to the alignment housing with a peelable adhesive bond such thatthe cover material may be peeled off just prior to use with a tab orother extension that a user may grasp. The cover material may be usefulfor maintaining the stacked array of pipette tips contained within thedevice during shipment as well as preventing contamination of containedpipette tips.

In some embodiments, the inside transverse dimensions of the proximalopening 48 of the alignment housing 22 should be a close fit with notmore than about a 0.005 inch to about a 0.05 inch gap between theoutside surface of the perimeter of the loading block 26 to be used andthe inside surface of the proximal opening 48. This controlled fit maybe used to assure that the restrictive apertures 32 of the barrier plate28 are properly aligned with the channels 34 of the loading block 26. Itmay generally be undesirable for the outer surface perimeter of theloading block 26 to have snug fit with the inside surface of thealignment housing 22 as this might make removal of the pipette tipdispensing device from the loading block 26 difficult.

The substantially planar barrier element in the form of the barrierplate 28 is disposed at a top portion of the alignment housing 22substantially perpendicular to the sides of the alignment housing andsubstantially parallel to the actuator plate 18 of the actuator. Thebarrier plate 28 includes a plurality of the restrictive apertures 32 inan array which is substantially aligned with respective proximalalignment members 16 of the actuator plate 18. The restrictive apertures32 are configured to engage an outside surface of a pipette tip,restrict lateral displacement of a pipette tip and resist axialdisplacement of the pipette tip until an axial threshold force isimparted to the pipette tip. Once the threshold axial force is reached,a pipette tip 20 may pass through the restrictive aperture and beejected into the corresponding loading channel 34 of the loading block26 disposed below the restrictive aperture 32. As soon as the majortransverse dimension of the pipette tip 20 clears the barrier plate 28,gravitational force on the pipette tip 20 moves the tip 20 into thechannel 34 in a distal or downward direction until the major transversedimension or proximal end of the pipette tip registers on the edge ofthe channel 34 in the loading block 26.

The barrier plate 28 may be secured around its perimeter to an upperedge or rim of the alignment housing by welding, adhesive bonding or anyother suitable method. The barrier plate 28 may have a thickness andmaterial rigidity sufficient to prevent significant deformation upon theapplication of actuation force to the pipette tips 20 disposed in theplate 28. As such, the barrier plate 28 may have a thickness of about0.05 inches to about 0.3 inches, more specifically, about 0.1 inches toabout 0.25 inches. For some embodiments, the barrier plate 28 may bemade from suitable metal, such as aluminum, or polymers such aspolypropylene, polycarbonate, polyethylene, polystyrene, polyurethaneand the like as well as any other suitable polymers that may be molded,thermoformed or the like. For some embodiments, the barrier plate 28 mayhave a length of about 2 inches to about 6 inches and a width of about 1inch to about 3 inches.

For some embodiments, the restrictive apertures 32 of the barrier plate28 include holes through the barrier plate 28 that may have an innertransverse dimension sized and configured to have a mechanical fit orengagement having an interference fit with the major outer transversedimension 46 of the pipette tips 20 that are to be used with the device.The spacing of the array of restrictive apertures 32 may generally beconfigured to match the spacing and configuration of the alignmentmembers 16 of the actuator plate 18, which may also match theconfiguration of the array of channels 34 in a suitable loading block26. Such an interference fit requires that the restrictive aperture 32have an inner transverse dimension or diameter that is less than themajor outer transverse dimension 46 of the pipette tips.

This interference fit may be overcome by the application of a thresholdaxial force on a pipette tip 20 which is engaged with the restrictiveaperture 32. For some embodiments, the interference fit is overcome byelastic deformation, deflection or compression of the proximal end ormajor transverse dimension portion 46 of the pipette tip 20 as it isforced through the restrictive aperture 32. The more interference in thefit and the harder the shore hardness of the material of the pipette tip20, the greater the threshold force required to push the pipette tip 20through the restrictive apertures 32. For some embodiments, thisinterference fit may have an interference of up to about 0.003 inches,more specifically, up to about 0.002 inches. For some embodiments, therestrictive apertures 32 of the barrier plate 28 may have an innertransverse dimension or diameter of about 1 mm to about 9.1 mm. Therestrictive apertures 32 of the barrier plate 28 may have substantiallyparallel sides, be configured with tapered sides, have chamfered edgesor edges with a radius or any other suitable configuration.

Vertical spacing between the top of the barrier plate 28 and the top ofthe loading block 26, as shown by arrow 52 in FIG. 5A, may be configuredsuch that a distal end or distal portion of a pipette tip 20 which isengaged with a restrictive aperture of the barrier plate 28 is disposedwithin a hole or channel 34 of a loading block 26 so long as thatloading block is engaged with the alignment housing 22. In thisarrangement, the pipette tips are preloaded into the holes or channels34 of the loading block 26. After being ejected from the barrier plate28 once a threshold axial force has been applied them, they willcontinue down into the channels 34 of the loading block 26. Such distaltip engagement of the pipette tips into the channels 34 of the loadingblock 26 reduces or prevents potential jams or mis-feeds of the pipettetips after ejection from the restrictive apertures 32 of the barrierplate 28.

For some embodiments, the vertical distance between the bottom of thebarrier plate 28 and the bottom of the alignment housing 22 as well asthe vertical spacing between the proximal actuator plate 18 and thebottom of the actuator housing 12 may be important. In particular, forsome embodiments, these distances may be selected or otherwiseconfigured such that the actuator housing 12 may be depressed down farenough to allow the last array of pipette tips 20 engaged directly withthe proximal alignment members 16 of the proximal alignment plate 18 tobe forced through the barrier plate 28 and into a loading block 26, asshown in FIG. 5B before the bottom of the actuator housing 12 contactsthe working surface 50 upon which the loading block 26 and alignmenthousing 22 are disposed.

In use, an array of multiple pipette tips 20 may be dispensed into aloading block 26, with the pipette tip dispensing device embodimentsdiscussed herein. For some embodiments, the dispensing device 10 isprovided loaded with a regularly spaced array of 8×12 columns of pipettetips nested with 3 pipette tips in each column as shown in FIG. 5A andin more detail in FIG. 6A. The nested, regularly spaced array may bedisposed between any or all of the respective proximal alignment members16 and corresponding restrictive apertures 32 with a longitudinal axis36 of each nested column of pipette tips being substantially aligned andcoaxial with the respective proximal alignment members 16 andrestrictive apertures 32. The proximal opening 48 of the alignmenthousing 22 may then be placed over and engaged with a loading block 26such that distal ends of the distal most pipette tips 20 of each column,which are engaged with restrictive apertures of the barrier member 28,are disposed within channels 34 of the loading block 26 again as shownin FIG. 6A. Also, the outer perimeter surface of the loading block 26 isengaged with or otherwise laterally constrained by the inner surface ofthe alignment housing 22 to prevent substantial relative lateralmovement between the loading block 26 and the alignment housing 22. Oncethe dispensing device 10 is so engaged with the loading block 26, theactuator may be actuated so as to apply an axial force on the array ofcolumns of pipette tips 20 engaged with the restrictive apertures 32.

For some embodiments, the axial force of the actuation may be generatedby manually applying a downward force on an upper outside surface of theactuator housing 12. The force on the actuator housing 12 is thentransferred to the actuator plate 18 and proximal alignment members 16thereof, which, in turn, transmits the axial force to the nested columnsof pipette tips 20. The manually applied force on the actuator housing12 is continued until a threshold axial force is achieved so as todeform the major transverse portions 46 of the pipette tips 20 engagedwith the restrictive apertures 32 of the barrier plate 28. As the forceis applied, the proximal portions and major transverse dimensionportions 46 of the pipette tips 20 may be elastically deformed andforced through the restrictive apertures 32 so as to eject the row orarray of pipette tips engaged with the restrictive apertures intorespective channels 34 in the loading block 26 as shown in FIG. 6B withthe proximal major transverse dimension portion 46 of the pipette tipsengaging the top surface of the channels 34 of the loading block 26.

Once the distal most array of pipette tips 20 are dispensed into theloading channels 34 of the loading block 26, the next row of pipettetips 20 move down into the restrictive apertures 32 of the barrier plate28 and come to a stop as the major transverse dimension portions 46 ofthose pipette tips 20 engage the restrictive apertures 32. The downwardprogress of the actuator housing 12 and actuator plate 18 is alsoresisted by the engagement of corresponding detent members of theactuator housing 12 and alignment housing 22 at the end of the actuationstroke or step. The dispensing device 10 may then be lifted from thefully loaded loading block 26 so as to expose the newly loaded pipettetips 20. In addition, the loading block 26 may then be transferred toanother location for use of the newly loaded pipette tips 20.

For dispensing device embodiments having the array of nested columns ofpipette tips disposed therein, this process may be repeated byre-engaging the alignment housing 22 with empty loading blocks 26 at thebeginning of each loading cycle and the actuator depressed so as to loada new set of pipette tips 20 into the empty block. As the last array ofpipette tips 20 are ejected from the barrier plate 28, the proximalalignment elements 16 may be configured to engage and enter therestrictive apertures 32 of the barrier plate 28 so as to assureejection of the final row of pipette tips 20 from the barrier plate.

During the dispensing process, if the actuator housing 12 and alignmenthousing 22 comprise a clear or translucent material, such as a clear ortranslucent polymer material, the ejection of the array of multiplepipette tips 20 from the restrictive apertures 32 of the barrier member28 may be visualized during actuation. For manually actuated processes,the alignment housing 22 of the device 10 may be manually placed overand engaged with loading blocks 26 as needed. The pipette tip dispensingdevice 10 may also be manipulated by a robotic positioning device (notshown) such as a three axis to six axis robotic positioning device thatmay be configured to engage the alignment housing 22 with an emptyloading block 22, actuate the actuator of the dispensing device 10,remove the dispensing device 10 from the loading block 26 that is newlyloaded with pipette tips 20, remove the loaded loading block 26 andreplace it with an empty loading block 26 and repeating the process.

Once the pipette tips 20 are loaded into the loading block 26 as shown,the pipette tips 20 may then be engaged with a pipettor device, such aspipettor device 44. FIGS. 8 and 9 show a loading block 26 with a pipettetip 20 disposed in a loading channel 34 of the block 26 and a nozzle 54of a pipettor 44, such as the pipettor 44 of FIG. 7, engaged with theproximal port of the pipette tip 20. When the pipettor nozzle 54 isengaged with the proximal port of the pipette tip 20, the pipettor 44may then be used for any of the applications discussed herein as well asany other suitable applications. Once the pipette tip 20 on the pipettordevice 44 has been used, it may be ejected from the pipettor device 44and replaced with a new pipette tip 20 from the loading block 26 and theprocess repeated.

For automated method embodiments, an array 56 of multiple nozzles 54 ofa robotic or automated pipettor device 58 may be engaged simultaneouslywith an array of pipette tips 20 as shown in FIG. 10. Such a loadingblock 26 may be loaded with the array of pipette tips 20 with thedispensing device 10 of FIG. 1. Once the pipette tips 20 disposed on theautomated pipettor device 58 have been used for the intendedapplication, they may be ejected from the pipettor device 58 anddisposed of. A new set of pipette tips 20 may then be loaded onto thenozzles 54 pipettor device 58 from a freshly filled loading block 26which has been filled by dispensing device 10. Such an automated processis facilitated by the use of the pipette tip dispensing device 10 orother similar embodiments as the loading blocks 26 may be quickly andconveniently refilled with a new array of pipette tips 20 without theneed to transfer a loading plate or tray from the pipette tip packaging.

FIGS. 11 and 12 illustrate an embodiment of a pipette tip dispensingdevice similar in many respects to the dispensing device embodiment 10of FIG. 1, except that the actuator housing of the embodiment includes atelescoping configuration that allows for the storage and dispensing ofa greater amount of nested pipette tips disposed in a regularly spacedarray. The dispensing device 60 of FIGS. 11 and 12 includes an alignmenthousing 22 that may have features, dimensions and materials that are thesame as or similar to those of the alignment housing 22 of FIG. 1,including the details of the barrier plate 28 and proximal opening 48which may be configured to engage a loading block 26 in the same manneras the proximal opening 48 discussed above. The proximal opening or port48 may also include a polymer peelable cover sheet over the proximalport such as the cover discussed above. The telescoping nature of theactuator housing, however, may be configured to allow a greater numberof pipette tips 20 to be disposed in a nested stacked array between therespective proximal alignment members 16 and restrictive apertures 32 ofthe barrier plate 28.

The particular embodiment of the dispensing device 60 shown in FIG. 1 isshown with 3 nested, stacked pipette tips 20 and the embodiment of FIG.11 is shown accommodating 5 nested, stacked pipette tips 20 when in anextended state. Although these embodiments are shown to accommodatearrays of 3 and 5 nested pipette tips, the respective devices 10 and 60may also be configured to accommodate a different number of nestedpipette tips depending the housing configurations and dimension of thepipette tips 20 being used. Arrays of nested pipette tips stacked fromabout 2 pipette tips per stack to about 30 pipette tips per stack may beused, more specifically, about 3 pipette tips per stack to about 20pipette tips per stack, and even more specifically, about 4 pipette tipsto about 10 pipette tips, may be used.

The actuator housing includes a proximal housing member 62 and a distalhousing member 64 that is vertically displaceable within the proximalhousing member 62. The distal housing member 64 has no top portion andhas an inside surface configured to slidingly engage the outer lateralsurfaces of the alignment housing 22 in a manner similar to theengagement between the alignment housing 22 and actuator housing 12discussed above. FIG. 12 illustrates the pipette tip dispensing device60 of FIG. 11 in a collapsed state with all pipette tips 20 having beendispensed from the device and the proximal alignment members 16 of theproximal actuator housing 62 engaged with the respective restrictiveapertures 32 of the distal barrier plate 28. The detent members 14 and24 of the proximal actuator housing 62, distal actuator housing 64 andalignment housing 22 are also engaged in this collapsed state. Theconstruction of the proximal actuator housing member 62 and distalactuator housing member may have the same or similar features,dimensions and materials as those of the actuator housing 12 andalignment housing 22 discussed above for some embodiments.

A pipette tip unit is arranged in an array of pipette tip units in someembodiments. Each unit has a plurality of nested pipette tips, and unitsare arranged in an array in certain embodiments. The relativeconfiguration of nested pipette tips often is determined where a firstportion of an inner surface of a first pipette tip interferes with asecond portion of the outer surface of a second pipette tip nesting inand above the first pipette tip (e.g., the inner diameter of the firstportion is about equal to the outer diameter of the second portion).Pipette tips can be dispensed as an array of pipette tips one pipettetip (i.e., one level) high. For example, a pipette tip array can fillall the holes in a loading block. When a device of the present inventionis filled with an array of pipette tip units and actuated, a one-layerpipette tip array would be ejected into an empty loading block 26, thusfilling it, in some embodiments. Each pipette tip unit comprises 2, 3,4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or more nested pipette tips in someembodiments. The pipette tips often are nested continuously, and thereoften are no intermediate plates or intermediate components between thenested pipette tips.

FIGS. 13 and 14 illustrate an embodiment of a pipette tip dispensingdevice distal barrier plate 70 having a plurality of channels 76, whereeach channel has a diameter larger than the widest portion of a pipettetip, which can be the major outer transverse dimension 46 of a pipettetip or the largest outer diameter of the proximal portion of a pipettetip. The barrier plate 70 in FIGS. 13 and 14 has a substantially flattop surface 82, and a substantially flat bottom surface 73 that has aplurality of tails 74 around some or all of channels 76. The bossedarrangement of substantially flat surface 73 having a thickness 79 inconjunction with substantially flat surface 72 is optional, and surface73 may be continuous to the perimeter of the plate in some embodimentswith no bossed region. FIG. 13B illustrates tails 74 extending in anearly perpendicular orientation from the flat bottom surface 72. Thetails 74 around each channel 76 contact the pipette tip, and optionallydeflect outwards against the proximal portion of a pipette tip, when apipette tip is dispensed and passes by the tails 74, thereby imparting africtional force on the pipette tip when it is dispensed. Distal barrierplate 70 also includes tails 74 with inner surface 75 and optional pins71.

Each channel can have 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15,16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 or moretails. FIGS. 13 and 14 illustrate an embodiment of the barrier platehaving four tails 74 per channel. FIG. 13 Illustrates an embodiment ofthe barrier plate where each channel of the barrier plate comprisestails of the same length. FIG. 13B shows an enlarged view of eachchannel with tails of the same length. FIG. 13C shows a profile view ofthe tails 74 where they are all of the same length in the barrier plate.FIG. 14C shows an example of channels of the barrier plate having tailsof different lengths, where tail 78 is shorter than tail 80. Channelslocated in the center of the barrier plate can also be the shortertails, as seen in FIG. 14C. Subsequent channels concentrically disposedabout a central longitudinal axis can have progressively longer tails,also seen in FIG. 14C. In some embodiments channels located in thecenter of the barrier plate can have the longest tails, and in certainembodiments, subsequent channels concentrically disposed about a centrallongitudinal axis can have progressively shorter tails, which is notshown in FIG. 14C.

Downward movement of the pipette tips within the housing often isachieved by pressure or force, not gravity in most embodiments, anddownward movement often is actuated by a user. Downward force orpressure often begins with user-induced activation from the center topof the housing device, with the pressure or axial force greatest at thevertical center. The pressure or axial force then spreads peripherallyto the side walls of the housing as well as spreading horizontally,peripherally to the edges of both activator and distal barrier plates.

A user may actuate the device several times, unloading or ejecting anarray of pipette tips from the bottom of the distal barrier plate eachtime. Pipette tips may be dispensed until, for example, the device isempty of pipette tips; insufficient axial force is placed on the device;a force is applied by a user that racks the housing, activator plateand/or distal barrier plate such that pipette tips are not ejected;and/or the actuator housing is at ground level.

It has been determined that providing a distal barrier plate thatreleases pipette tips in an array at different times is advantageous. Adistal barrier plate in which all channels have the same frictionalprofile ejects all tips of an array at the same time, which requires aparticular actuating force by the user or operator, referred tohereafter as total force or “F_(T)” A distal barrier plate in which somechannels have a different frictional profile compared to other channels,however, ejects tips in an array at different times. Without beinglimited by theory, a portion of force F_(T) first ejects one subset ofpipette tips in the array through channels having a first frictionalprofile, and another portion of F_(T) then ejects a second subset ofpipette tips in the array through channels having a second frictionalprofile. Thus, releasing tips in an array at different times effectivelyspreads out F_(T) over time, and effectively reduces the actuating forcerequired to eject tips of an array at any one point of time.

The term “same frictional profile” as used herein refers to channels ina distal barrier plate that apply the same frictional force to pipettetips in an array for the same amount of time. The term “differentfrictional profile” refers to a channel in a distal barrier plate thatapplies a different frictional force and/or applies the same ordifferent frictional force to a pipette tip for a different amount oftime, as compared to another channel in the plate.

In some embodiments, a distal barrier plate includes a subset ofchannels that ejects pipette tips at a rate different than anothersubset of channels. In certain embodiments, a distal barrier plateincludes 2 to 100 different subsets of channels, each of which eject apipette tip of one array at a different time (e.g., 3, 4, 5, 6, 7, 8, 9,10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55,60, 65, 70, 75, 80, 85, 90, 95 different subsets). Thus, a distalbarrier plate can include 2 to 100 different subsets of channels, eachof which have a different frictional profile. The time lapse between thetime one set of tips is released from one subset of channels to the timeanother set of tips is released from another subset of channels can bebetween about 0.00001 seconds to about 5 seconds (e.g., 0.0001, 0.001,0.01, 0.1, 1 second), and the total time required to eject pipette tipsin an array can vary from about 0.001 seconds to about 5 seconds (e.g.,0.01, 0.1, 1 second). In some embodiments, a distal barrier plate isprovided in which all channels have the same frictional profile and alldispense pipette tips at the same time.

In some embodiments, pipette tips at or near the center of a distalbarrier plate eject first, and pipette tips near the edge of a distalbarrier plate eject last. In certain embodiments, subsets of channelsdisposed in a linear and/or radial orientation away from the center tothe periphery of the plate sequentially eject tips at progressivelyincreasing times.

In certain embodiments, pipette tips at or near the center of a distalbarrier plate are ejected last, and pipette tips at or near the edge ofa distal barrier plate are ejected first. In such embodiments, subsetsof channels disposed in a linear and/or radial orientation from theperiphery of the plate to the center of the plate sequentially ejecttips at progressively increasing times.

Where it is noted herein that a channel applies a particular frictionalforce to a pipette tip for particular period of time, the channelperiphery or channel walls may apply a frictional force to the pipettetip. Often, however, a feature outside a channel applies a frictionalforce to the pipette tip (e.g., projections or tails around a channel inconnection with a top and/or bottom surface of the plate).

Certain features of a distal barrier plate can apply a particularfrictional force to a pipette tip. For example, channel features,including but not limited to channel diameter; channel texture; thepresence or absence of one or more projections in the channel (e.g.,connected to a channel interior wall); the shape, size, length,thickness, width, rigidity, texture, and/or angle of one or moreprojections in a channel; or combination of the foregoing, can affectthe frictional force applied to a pipette tip as it is ejected. Also,the presence or absence of one of more projections outside a channel(e.g., connected to top and/or bottom surface of a distal barrierplate); the shape, size, length, thickness, width, texture and/or angleof one of more projections outside a channel, or a combination of theforegoing, can affect the frictional force applied to a pipette tip asit is ejected.

Any suitable number of projections can be present around or near achannel, including without limitation about 1 to about 50 projections.Projections can contact one or more surfaces of a pipette tip, in someembodiments. Projections can contact the widest portion (e.g., largestdiameter portion) of a pipette tip (e.g., proximal region portion), andsometimes do or do not contact lower diameter portions of a pipette tip(e.g., distal region portion). Projections sometimes flex against aportion of a pipette tip (e.g., proximal region portion) when thepipette tip is dispensed past the projections. Projections in someembodiments are elastic, and can return to about the same position aftera pipette tip is ejected. Projections in connection with the top surfaceor bottom surface of a distal barrier plate sometimes are referred toherein as “tails,” as described herein.

Projection or tail length can affect the time at which pipette tips areejected. Without being limited by theory, tails having a relativelylonger length apply a frictional force for a longer period of time andresult in a tip ejection time that is longer than for relatively shortertails. FIGS. 14A and 14C show channels located in the center of thebarrier plate along the X axis can have tails of the same length andchannels along the Y axis can have tails of varying length. In someembodiments, channels located in the center of the barrier plate alongthe Y axis can have tails of the same length and channels along the Xaxis can have tails of varying length or channels located in the centerof the barrier plate along the X and Y axes comprise tails of varyinglength, which is not shown. Channels can have an even or odd number oftails. For channels having even number of tails, the tails directlyopposite one another around a channel can have the same length. And incertain embodiments tails directly opposite one another around a channelcan have a different length. Tails adjacent to one another can also havea different length. The tails can be between 0.01 μm-2.0 mm in length.The tails can be between 0.05 μm-2.0 mm in length. The tails can beabout 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.12,0.14, 0.16, 0.18, 0.2, 0.22, 0.24, 0.26, 0.28, 0.30, 0.32, 0.34, 0.36,0.38, 0.4, 0.42, 0.44, 0.46, 0.48, 0.5, 0.52, 0.54, 0.56, 0.58, 0.6,0.62, 0.64, 0.66, 0.68, 0.7, 0.72, 0.74, 0.76, 0.78, 0.8, 0.82, 0.84,0.86, 0.88, 0.9, 0.92, 0.94, 0.96, 0.98, 1.0, 1.2, 1.4, 1.6, 1.8, or 2.0mm in length, in certain embodiments. A distal barrier plate in someembodiments may include tails having different lengths at differentchannels (e.g., tails around a first channel have a first length, andtails around a second channel have a second length). For example, incertain embodiments the length of tails for each channel progressivelyincreases or decreases (i) from the center of the X-axis to each end ofthe X-axis and/or (ii) from the center of the Y-axis to each end of theY-axis. As used herein, the term “progressive” refers to linear,stepwise, sigmoidal, and exponential, in particular embodiments.

The internal angle of projections or tails also can affect the time atwhich pipette tips are ejected. For example, a relatively smallerinternal angle for tails or projections can result in a relativelylonger time required to eject a pipette tip. The term “internal angle”as used herein with respect to a tail around a channel is an anglemeasured from the midpoint of a channel at the bottom surface of theplate towards the tail surface facing the channel (e.g., surface 75 inFIG. 13D), as illustrated in FIG. 13D as angle theta. For example, aninternal angle of 90° from the bottom surface 72 of the distal barrierplate would be exactly parallel to the Z axis as shown in FIG. 13C.Tails of the barrier plate often are nearly perpendicular with respectto, and often are at an internal angle of almost 90° from, the bottomsurface 72 of the distal barrier plate. In some embodiments, tails 74are at an internal angle of about 89° to about 80° from the bottomsurface 72 of the distal barrier plate. Tails can be at an internalangle between 88-85°, 87-84°, 86-83° or 86-85° from the bottom surfaceof the distal barrier plate. Tails are at an internal angle of about 87°from the bottom surface of the distal barrier plate in some embodiments.A distal barrier plate in some embodiments may include tails havingdifferent angles at different channels (e.g., tails around a firstchannel have a first internal angle, and tails around a second channelhave a second internal angle). For example, in certain embodiments theinternal angle of tails for each channel progressively increases ordecreases (i) from the center of the X-axis to each end of the X-axisand/or (ii) from the center of the Y-axis to each end of the Y-axis.

Texture of tails or projections can affect the time required to eject apipette tip from a distal barrier plate. In some embodiments, texturecan modulates the length, thickness or angle of a tail. Tails cancomprise smooth surfaces in some embodiments, and in certainembodiments, tails can comprise texture on one or more surfaces. A tailcan be entirely smooth, may be entirely textured, or may includetextured and smooth surfaces, in some embodiments. A plate can comprisetails that are smooth and some tails that comprise texture. Tail texturecan include, without limitation, ridges, barbs, grooves, grains,embossed, etches, pores, pits, lines, scratches, scores, scrapes, cuts,carvings, incisions and the like. Tail texture can increase frictionalforce on pipette tips moving past the tails when dispensed. Texture alsocan aid in channeling pipette tips through the tails and into theloading block 26 (e.g., linear or twisted grooves (e.g., rifled grooves)extending from a tail top to tail bottom). A distal barrier plate insome embodiments may include tails having different textures atdifferent channels (e.g., tails around a first channel have a firsttexture that applies a first frictional force to pipette tips, and tailsaround a second channel have a second texture that applies a secondfrictional force to pipette tips). For example, in certain embodimentsthe texture of tails for each channel progressively increases ordecreases the frictional force (i) from the center of the X-axis to eachend of the X-axis and/or (ii) from the center of the Y-axis to each endof the Y-axis.

Tails around a channel often are not in the channel, and the portion ofa tail joined to the distal barrier plate bottom surface sometimes isco-extensive with the edge of a channel. In some embodiments, the baseportion of a tail joined to the distal barrier plate bottom surface isdisplaced a distance from the channel perimeter that it surrounds, whichdistance can be a mean, nominal, average or maximum distance of about0.001 millimeters to about 2 millimeters (e.g., the portion of the tailclosest to the channel perimeter that the tail surrounds is offset0.005, 0.01, 0.05, 0.1, 0.5 or 1 millimeters from the perimeter). Theterm “displaced” as used herein with respect to tail orientation refersto displaced away from channel perimeter such that the tail base ispartially over the channel perimeter, or displaced away from the channelperimeter so that there is a gap between the channel perimeter and thetail base on the plate bottom surface equal to the displaced distance.Thus, the term “surrounds” as used herein with respect to a tail refersto a tail associated with a channel, where the tail base is co-extensivewith, or displaced towards or away from, the channel perimeter. Forexample, tail 74 surrounds channel 76, and tail 74′ surrounds channel76′, but tail 74 does not surround channel 76′, as shown in FIG. 14B.

Tails described herein generally are not prone to breakage as pipettetips are dispensed through a distal barrier plate comprising the tails.Without being limited by theory, the nearly perpendicular orientation oftails with respect to the bottom surface of a distal barrier platecontributes to tail stability, as this orientation requires littleflexion of tails to apply a force to the pipette tips. In certainembodiments, the maximum, mean, median or nominal tail flexion is about0.01 degrees to about 10 degrees (e.g., about 0.05, 0.1, 0.5, 1, 2, 3,4, 5, 6, 7, 8, 9 degrees). The term “flex outward” as used herein refersto a tail flexing a certain number of degrees added to the internalangle. For example, a tail that flexes outwards by 2 degree adds 2degrees to the internal angle in the flexed state; if the tail in theunflexed state has an internal angle of 87 degrees, the tail in theflexed state has an internal angle of 89 degrees. In certainembodiments, no more than 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 tails, orportions thereof, are separated from the distal barrier plate for a setof 480 pipette tips dispensed through the plate.

A tail may have any convenient shape. A surface of a tail, can be of ashape that includes without limitation, square, rectangle, rhombus,parallelogram, circle, oval, arced, curved, planar, non-planar, and thelike. The thickness of a tail can be continuous or tapered (e.g.,tapered towards the top (i.e., in association with the plate) or bottom(i.e., at the tail terminus) of the tail).

In some embodiments, the housing can have an actuator housing with a topportion, four sides, an inner surface, and a plurality of regularlyspaced detent members disposed on at least one side of the housing, andan alignment housing with an outside surface in contact with the insidesurface of the actuator housing in a sliding arrangement, a plurality ofregularly spaced detent members configured to releasably engage thedetent members of the actuator housing and having a regular spacing thatis substantially the same as the regular spacing of the detent membersof the actuator housing, and a proximal opening having an inside surfaceconfigured to engage outer lateral sides of a loading block 26.

The housing can be made from a polymer material. The polymer material ofthe housing can be molded polypropylene, or any suitable polymer,including, but not limited to polyethylene (PE), high-densitypolyethylene, low-density polyethylene, polyethylene teraphthalate (PET,e.g., bio-PET), polyvinyl chloride (PVC), polyethylenefluoroethylene(PEFE), polystyrene (PS), high-density polystryrene, acrylnitrilebutadiene styrene copolymers, crosslinked polysiloxanes, polyurethanes,(meth)acrylate-based polymers, cellulose and cellulose derivatives,polycarbonates, ABS, tetrafluoroethylene polymers, correspondingcopolymers and the like, and combinations of the foregoing. The polymermaterial of the housing can have a thickness of about 0.005 inches toabout 0.05 inches. The actuator housing can have a telescopingarrangement having multiple housing elements.

The alignment housing can have an optional flange that serves as afooting, in some embodiments. The flange can add extra stability to thehousing and can help to ground the housing unit so that no unwantedhorizontal movement can occur.

The actuator plate 18 can have a member on the top portion of theactuator that maintains contact with and restricts lateral displacementof the proximal portion of the pipette tips. The member can be selectedfrom the group consisting of foam, a raised grid, a plurality ofproximal alignment members 16 and the like. FIG. 1 shows the proximalalignment members 16 on the top portion of the activator plate 18. Theproximal alignment members can aid in aligning stacked columns ofpipette tips to each channel in the distal barrier plate, which isassociated with each empty hole in a loading block 26 where an ejectedpipette tip is placed. The member selected can be any material orcombination of materials known to one of skill in the art. The member isplaced to prevent unwanted vertical or horizontal movement of thepipette tips during storage or activation of the device.

Static charge can develop on pipette tips during use or shipping. Thisstatic charge can remain on the tips as they reside in dispensers ortrays because there often is no flow or discharge of the electric chargefrom the tips to a ground source. Static charge in/on the tips and othercomponents of a tray or dispenser may cause some of the tips to repelaway from each other and other tray or dispenser components. Thisrepulsion can result in the tips arranged in a different orientationthan intended, and can negatively impact interaction with pipettedevices (e.g., automated dispensers).

In certain embodiments, the pipette tips are in contact with anelectrically conductive member, or a portion thereof, which is incommunication with the exterior of the housing. This contact can allowstatic charge from the pipette tips to be discharged. The contact of anelectrically conductive member, or a portion thereof, sometimes is withtop proximal edges of tips, which may involve direct, indirect, and/oreffective communication with the inner portion of the housing, activatorplate, distal barrier plate, loading block, combination thereof, orcomponent thereof. The contact sometimes is with the sides of tips whichmay be in direct, indirect, and/or effective communication with thehousing, activator plate, distal barrier plate, loading block,combination thereof, or component thereof. In some embodiments, anelectrically conductive member, or a portion thereof, is in direct,indirect, and/or in effective communication with the pipette tips whichultimately aids in discharging the static charge in/on the pipette tips.The electrically conductive member, or a portion thereof, may be ineffective communication with any component or components of the deviceand be in effective communication with the exterior housing. In certainembodiments, an electrically conductive member, or a portion thereof, islocated in any of components of the device such as for example, theactuator housing, alignment housing, activator plate, distal barrierplate, channel, tail and the like, or a component thereof, or acombination of the foregoing, that is in effective communication withthe pipette tips, and is exposed through the housing sides or flanges.

An electrically conductive member may comprise any type of electricallyconductive material known, such as a conductive metal, for example.Examples of conductive metals include, without limitation, platinum(Pt), palladium (Pd), copper (Cu), nickel (Ni), silver (Ag) and gold(Au). The metals may be in any form in or on the conductive member, forexample, such as metal flakes, metal powder, metal strands or coating ofmetal. An electrically conductive member, or portions thereof, maycomprise a metal, polymeric material, foam, film, sheet, foil, salt orcombinations thereof. In some embodiments, a conductive metal foil maybe utilized for one or more components of a pipette tip device (e.g.,copper-aluminum foil; label adhered to an electrically conductive tab onexterior of the housing component). The electrically conductivematerials, or portions thereof, may be any material that can containmovable electric charges, for example such as carbon. In someembodiments, the electrically conductive member comprises about 5% toabout 40% or more carbon by weight (e.g., 7-10%, 9-12%, 11-14%, 13-16%,15-18%, 17-20%, 19-22%, 21-24%, 23-26%, 25-28%, 27-30%, 29-32%, 32-34%,33-36%, or 35-38% carbon by weight). In certain embodiments, anelectrically conductive film is utilized that includes carbon (e.g.,commercially available from Gemini Plastic Enterprises, Inc.,California). An electrically conductive film in some embodimentscontains ethylene vinyl acetate (EVA), which can impart a supple qualityto the film (e.g., about 5% to about 25% EVA by weight; about 6, 7, 8,9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24% EVA). Insome embodiments a conductive tab may be in effective communication withany one or combination or all of the components of the device and aid indischarging an electrical charge from the device. A tab often is ineffective communication with a conductive material contacting thepipette tips and the exterior of the device (e.g., exterior surface ofthe housing). The tab may be affixed to one or more portions of a device(e.g., by an electrically conductive label).

The term “effective communication” as used herein refers to direct(e.g., part of the conductive member) or indirect (e.g., via componentnot part of the conductive member) in communication with exterior of thehousing. The term “exposure of conductive member” as used herein mayrefer to exposure by a reveal in a plate or member which may extend tothe housing exterior or can be free hanging or may be affixed to anexternal surface of the housing and/or loading block. The externalsurfaces of the housing are for example the sides or bottom of theactuator or alignment housing. The external surfaces of the housing arefor example the roof or sides of the housing. The term “affixed” as usedherein refer to attachment for example such as embossed or adhesive.

The entirety of each patent, patent application, publication anddocument referenced herein hereby is incorporated by reference. Citationof the above patents, patent applications, publications and documents isnot an admission that any of the foregoing is pertinent prior art, nordoes it constitute any admission as to the contents or date of thesepublications or documents.

Modifications may be made to the foregoing without departing from thebasic aspects of the invention. Although the invention has beendescribed in substantial detail with reference to one or more specificembodiments, those of ordinary skill in the art will recognize thatchanges may be made to the embodiments specifically disclosed in thisapplication, yet these modifications and improvements are within thescope and spirit of the invention.

The invention illustratively described herein suitably may be practicedin the absence of any element(s) not specifically disclosed herein.Thus, for example, in each instance herein any of the terms“comprising,” “consisting essentially of,” and “consisting of” may bereplaced with either of the other two terms. The terms and expressionswhich have been employed are used as terms of description and not oflimitation, and use of such terms and expressions do not exclude anyequivalents of the features shown and described or portions thereof, andvarious modifications are possible within the scope of the inventionclaimed. The term “a” or “an” can refer to one of or a plurality of theelements it modifies (e.g., “a reagent” can mean one or more reagents)unless it is contextually clear either one of the elements or more thanone of the elements is described. The term “about” as used herein refersto a value within 10% of the underlying parameter (i.e., plus or minus10%), and use of the term “about” at the beginning of a string of valuesmodifies each of the values (i.e., “about 1, 2 and 3” is “about 1, about2 and about 3”). For example, a weight of “about 100 grams” can includeweights between 90 grams and 110 grams. Further, when a listing ofvalues is described herein (e.g., about 50%, 60%, 70%, 80%, 85% or 86%)the listing includes all intermediate and fractional values thereof(e.g., 54%, 85.4%). Thus, it should be understood that although thepresent invention has been specifically disclosed by representativeembodiments and optional features, modification and variation of theconcepts herein disclosed may be resorted to by those skilled in theart, and such modifications and variations are considered within thescope of this invention.

Embodiments of the invention are set forth in the claim(s) thatfollow(s).

What is claimed is:
 1. A pipette tip dispensing device, comprising: (a)a housing configured to engage an outside perimeter of a loading block;(b) a distal barrier plate in connection with the housing; and (c) anarray of nested pipette tip units, each of which nested pipette tipunits is aligned with a channel in the distal barrier plate; whereby aone-layer pipette tip array is in the channels; which distal barrierplate comprises, a plurality of channels, each channels having adiameter larger than the widest portion of a pipette tip; two (2) ormore different subsets of channels; a substantially flat top surface;and a substantially flat bottom surface comprising a plurality of tailsaround the channels; wherein: the tails around any one subset ofchannels are the same length; tails around a subset of channels have alength different than tails around another subset of channels; the oftails around each channel are configured to contact and deflect outwardsagainst the proximal portion of a pipette tip when a pipette tip isdispensed and passes by the tails, thereby imparting a frictional forceon the pipette tip when it is dispensed; and the plurality of tailsaround one subset of channels is configured to eject pipette tipsthrough the one subset of channels at a time different than pipette tipsare ejected through another subset of channels.
 2. The device of claim1, wherein the array comprises 96, 384 or more pipette tip units.
 3. Thedevice of claim 1, wherein each nested pipette tip unit comprises two(2) or more nested pipette tips.
 4. The device of claim 1, wherein theplurality of tails around each channel comprises four (4) or more tails.5. The device of claim 1, wherein the plurality of tails extend about 90degrees from the flat bottom surface of the distal barrier plate.
 6. Thedevice of claim 5, wherein the plurality of tails are at an internalangle of about 89° to about 80° from the bottom surface of the distalbarrier plate.
 7. The device of claim 1, wherein the plurality of tailsaround each channel are not in the channel.
 8. The device of claim 1,wherein the housing comprises a polymer.
 9. The device of claim 8,wherein the polymer comprises molded polypropylene.
 10. The device ofclaim 8, wherein the polymer comprises a thickness of about 0.005 inchesto about 0.05 inches.
 11. The device of claim 1, wherein the tails areabout 0.01 micrometers to about 2.0 millimeters in length.
 12. Thedevice of claim 1, comprising an actuator plate disposed above thedistal barrier plate, wherein: (i) the distal barrier plate is disposedat a top portion of the housing; (ii) the actuator plate comprises aplurality of proximal alignment members configured to releasably engageand restrict lateral displacement of the pipette tip units; and (iii)the proximal alignment members are disposed substantially in a plane andin an array.
 13. The device of claim 12, comprising an actuator housingthat comprises a top portion, four sides, an inner surface, and aplurality of spaced detent members disposed on at least one side of theactuator housing.
 14. The device of claim 13, wherein the actuatorhousing comprises a polymer.
 15. The device of claim 13, wherein theinner surface of the top portion of the actuator housing comprises theactuator plate.